The discovery of thienamycin of formula I and analogous 1-carbapenem antibiotics derived from various strains of Streptomyces has resulted in an intense interest in the synthesis of the novel carbapenem skeleton.
Although a chiral synthesis of thienamycin starting from L-aspartic acid has been achieved by Salzmann et al. and is described in U.S. Pat. No. 4,290,947, this earlier work entailed a large number of steps and the use of strenuous reaction conditions which are not amenable to commercial production. Of particular concern was the chemistry used to elaborate a side chain at the 4-position of an azetidin-2-one compound.
The formation of a carbon-carbon bond at the 4-position of an azetidin-2-one compound opens up a wide variety of synthetic pathways to the carbapenems. The known methods, however, suffer from low yields, complex reaction conditions, and functional group limitations.